大鼠慢性溃疡性结肠炎模型的建立及操作规范探讨

Reproducing chronic ulcerative colitis in rats and its procedure conformity

关键词:  2,4,6-三硝基苯磺酸  葡聚糖硫酸钠  慢性溃疡性结肠炎  动物模型

Key words:  2, 4, 6-trinitrobenzenesulfonic acid  dextran sulfate sodium  chronic ulcerative colitis  animal model

摘要:

[目的] 建立大鼠慢性溃疡性结肠炎(UC)模型,探讨建立模型的操作规范。[方法] 雄性Wistar大鼠,除正常对照(NC)组,其余大鼠用100 mg/kg 2,4,6-三硝基苯磺酸(TNBS)/50%乙醇溶液建立溃疡性结肠炎急性模型,在造模10 d后,当所有模型大鼠便潜血转为“1+”时,随机抽取模型大鼠观察结肠病理组织学改变,剩余模型大鼠随机分为阳性对照(PC)组、UC组,用5%葡聚糖硫酸钠(DSS)水溶液或生理盐水进行致炎诱导结肠炎复发,造模后观察各组大鼠疾病活动指数(DAI),实验终点期处死观察结肠黏膜损伤指数(CMDI)及病理组织学改变。[结果] 与正常对照组比较,慢性溃疡性结肠炎组饮DSS后再次出现结肠炎发作,DAI及CMDI评分明显增高(P<0.05),而阳性对照组逐渐好转;病理组织学改变亦有显著差异。[结论] 采用TNBS/乙醇溶液首次致炎,用DSS间断进行诱导复发,可以模拟UC急性期与缓解期交替发作的特点,病理组织学改变与人类相似。

Abstract:

[Objective] To reproduce chronic ulcerative colitis (UC) in rats and establish its procedure conformity. [Methods] Male Wistar rats were randomly divided into normal control group and model group. Acute colitis was induced by rectal administration of 2, 4, 6-trinitrobenzenesulfonic acid solution (TNBS) dissolved in 50% ethanol, 100 mg/kg. Ten days later, when the stool occult blood of rats showed “1+”, ten model rats were randomly selected and killed to observe colon histological changes; the other model rats were randomly divided into positive (PC) group and (UC) group. The occurrence of colitis was induced with drinking 5% dextran sulfate sodium (DSS) solution or normal saline. After modeling the disease activity index (DAI) was observed in each group. The colonic mucosal damage index (CMDI) and the histological changes were assessed et the end on experiment. [Results] Compared with normal group and positive group, DAI and CMDI scores of chronic ulcerative colitis group were significantly increased (P<0.05); the histological changes were also differed significantly between them. [Conclusion] The chronic ulcerative colitis was successfully reproduced in rats. The method of using TNBS/alcohol solution to induce inflammation first and using DDS to induce its recurrence can imitate the characteristics of replaced onset of acute and chronic stage in UC group. It has similar pathological changes to that in human body.